论文标题

在上游和下游开放式阅读框之间的转换之间的非单向酮关系的确定性模型

A deterministic model for non-monotone relationship between translation of upstream and downstream open reading frames

论文作者

Andreev, D. E., Baranov, P. V., Milogorodskii, A., Rachinskii, D.

论文摘要

显示TASEP建模可为单个上游开放式阅读框(UORFS)在集成的应力响应期间上调下调下游翻译的实验确认能力提供了简约的解释。正如数值模拟所揭示的那样,该模型预测,在某些UORF上游降低扫描核糖体的密度会增加下游核糖体的流动。为了更好地了解确保上游和下游流之间的非符号酮关系的机制,在这项工作中,我们提出了一个现象学确定性模型,该模型近似于翻译过程的Tasep模型。我们确定了一个固定解的存在,该解决方案具有确定性模型沿UORF沿UORF的降低密度的存在。此外,我们发现上游核糖体密度与固定溶液的下游流之间有明确的非符号关系,该溶液的长度增加和日益渗漏的起始。 TASEP模型的固定分布,确定性模型的固定解和显式限制的固定解。

TASEP modeling was shown to offer a parsimonious explanation for the experimentally confirmed ability of a single upstream Open Reading Frames (uORFs) to upregulate downstream translation during the integrated stress response. As revealed by numerical simulations, the model predicts that reducing the density of scanning ribosomes upstream of certain uORFs increases the flow of ribosomes downstream. To gain a better insight into the mechanism which ensures the non-monotone relation between the upstream and downstream flows, in this work, we propose a phenomenological deterministic model approximating the TASEP model of the translation process. We establish the existence of a stationary solution featuring the decreasing density along the uORF for the deterministic model. Further, we find an explicit non-monotone relation between the upstream ribosome density and the downstream flow for the stationary solution in the limit of increasing uORF length and increasingly leaky initiation. The stationary distribution of the TASEP model, the stationary solution of the deterministic model and the explicit limit are compared numerically.

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